Study protocol

The study population in the Finnish Randomized Study of Screening for Prostate Cancer (FinRSPC) consists of 80,458 men born in 1929-1944 in the metropolitan areas of Helsinki and Tampere. Each year in 1996-1999, 8,000 men were randomized to screening, whereas the remaining approximately 12,000 men in the same birth cohorts formed the control group. In all, 32,000 men were randomized into the screening arm. This forms the largest component of the ERSPC, contributing 50% of the total of 162,000 men in the core age group in ERSPC. The first four-year screening round was carried out in 1996-99 and the second round in 2000-2003. The third and final screening rounds were performed in 2004-2007 with a smaller target population (excluding men aged >71 years). The men in the control arm were not contacted (except for surveys of quality of life). Prostate cancer (PC) incidence in the control group and among non-participants, as well as interval cancer post-screening incidence in the screening group is monitored through record linkage with the Finnish Cancer Registry.

A letter of invitation together with an information package, an informed consent form and a questionnaire regarding urological symptoms and treatment, as well as risk factors for prostate cancer was mailed to the men in the screening arm. The blood samples were analysed centrally at the Laboratory Diagnostics unit of Helsinki University Hospital. The PSA determinations were performed using the Hybritech Tandem-E assay, as in other centers participating in the European study. Quality control followed the guidelines provided by the collaborative study.

A screening positive finding was defined as a serum PSA concentration of 4.0 ng/ml or greater. Furthermore, men with serum PSA between 3.0 ng/ml and 3.99 ng/ml were referred to an additional test, which was digital rectal examination (DRE) in 1996-1999 and free to total PSA ratio <0.16 since 2000. Men with a screening positive finding were referred to the local urology clinic, including Helsinki University Hospital (with Peijas-Rekola Hospital, Jorvi Hospital) and Tampere University Hospital for diagnostic procedures including DRE, transrectal ultrasound (TRUS) and biopsy. The biopsy protocol initially comprised of sextant biopsy and with focal lesion also a directed biopsy and was modified in the fall of 2002 to decrease false negative biopsies so that 10 to 12 biopsies were performed (depending on prostate volume). As the trial is a multicenter study and has several hospitals with independent pathology, grading and staging of all cancers were re-assessed retrospectively by study pathologists (Paula Kujala and Marita Laurila). In addition, quality assurance of the pathology was conducted as a part of the European study led by prof van der Kwast (Erasmus University Rotterdam). Whole blood samples of all attenders have been stored for future analyses in the third screening round (N=13,806) and DNA has been extracted for men with and without prostate cancer in both arms for genetic analyses (N=4,976).

The screen-detected cancers are treated according to the established guidelines at the time of the diagnosis. It is crucial for comparability of the results to treat patients with similar disease with similar techniques in both arms, i.e. using similar treatment options given age, stage and grade. As new treatment options are developed and adopted, they will be incorporated to the protocol.

Participation ranged 68-70% in each round (with 23,771 men or 79% screened at least once). The proportion of screen-positive men increased from 10% to 13% and detection rate from 2.6% to 3.7% from the first to the third round. A total of 1,632 PC cases were detected by screening and 83% of them were low-risk cancers (cT1-T2, Gleason <7, PSA <10 ng/ml). The overall cumulative incidence of PC remains higher even 5 years after the last screening (8.5% vs. 10.3% at 15 years, HR=1.24), but this differs substantially by stage and grade – from a substantial excess in low-risk PC (RR=1.8) to reduction in advanced disease (RR=0.9 for high-risk PC and RR=0.6 for metastatic disease). The number of PC deaths up to 2012 (median follow-up of 15 years) is 651 (cumulative risk 0.8%).